Moreover, at the same dose, pregabalin significantly inhibited the visceromotor responses to phasic ascending CRD and increased the threshold pressure for response during the same CRD protocol or during continuous ramp (0�C80mmHg) CRD (data not shown). Altered colonic tone and accommodation to distension have been suggested either as contributing mechanisms to the altered colonic sensitivity observed in functional gastrointestinal disorders (Delgado-Aros and Camilleri, 2005). Therefore, an improvement in the pressure�Cvolume relationship during distension, reflected as shift to the left in the pressure�Cvolume relationship curves (that is, greater compliance and improved accommodation), might result in reduced pain sensitivity. Nevertheless, there is no clear correlation between compliance and pain perception.

For instance, intrarectal lidocaine reduced compliance in rats but had analgesic effects during CRD (K?ll et al., 2007), and the metabotropic glutamate 5 receptor (mGluR5) antagonist MPEP had analgesic effect during CRD without affecting colonic compliance (Lindstr?m et al., 2008). On the other hand, clonidine increased gastric and colonic compliance and also reduced pain perception (Thumshirn et al., 1999; Malcolm et al., 2000), and Wistar Kyoto rats with reduced colonic accommodation responses are also hypersensitive during CRD (Mart��nez et al., 2007). A recent report showed that pregabalin, in addition to increasing pain thresholds during CRD, also increased colonic compliance in IBS patients with colonic hypersensitivity (Houghton et al., 2007).

Similarly, in the present study, pregabalin, at a dose inducing clear analgesia, also modulated colonic compliance, with an increase in the volume response during CRD observed in five out of six animals tested. Altogether, these observations indicate that pregabalin increases colonic compliance in humans and animals. The potential relationship between the analgesic properties of pregabalin and its effects on compliance needs to be further characterized. In addition to its effects on pain, pregabalin has anxiolytic properties in both animals and humans (Huckle, 2004; Pohl et al., 2005; Rickels et al., 2005; Bandelow et al., 2007). Anxiety might be a contributing factor to the viscerosomatic and autonomic responses elicited by CRD. Therefore, anxiolytic effects of compounds might result in the reduction of pain-related readouts and be misinterpreted as analgesic activity. In this sense, other compounds (such as buspirone or mGluR5 antagonists) with potential anxiolytic activity also had analgesic effects in the CRD model in rats (Sivarao et al., 2004; Lindstr?m Cilengitide et al.